Apparatus for freeze-drying at atmospheric pressure



y 1963 H. T. MERYMAN 3,

APPARATUS FOR FREEZE-DRYING AT ATMOSPHERIC PRESSURE Filed Aug. 16, 1960 REFRIGERATION INVENTOR. HAROLD T. MERYMAN "Maw ATTORNEY United States Patent Ofi ice 3,096,163 Fatented July 2, 1963 3 096,163 APPARATUS FOR FREEZE-DRYING AT ATMOS- PHERIC PRESSURE Harold T. Meryman, Sandy Spring, Md., assignor to the United States of America as represented by the Secretary of the Navy Filed Aug. 16, 1960, Ser. No. 49,894 2 Ciaims. ((11. 3443) The invention described herein may be manufactured and used by or for the Government for governmental purposes without the payment of any royalty thereon.

This invention is directed to a process for freeze-drying at atmospheric pressure, and more particularly to a process for removing water or the like from liquid solutions, suspensions, or solvated solids.

Conventional methods of freeze-drying require that the liquid or solid to be freeze-dried be first frozen and then placed into a vacuum chamber. The heat to support sublimation is then provided in the vacuum chamber, as by conduction from a heated shell on which the container for the frozen material rests. The water vapor sublimating from the surface of the frozen material is generally condensed on a low temperature surface juxtaposed to the material. This process is a batch process and is relatively inefficient due to the limited rate at which heat can be introduced, since an excessive rate of heat input will melt the material where it touches the source of heat.

Furthermore, as drying progresses, the increased thickness of the dried shell overlying the drying boundary interferes with the passage of water vapor and further restricts the possible drying rate.

More recently, methods have been proposed in which the material to be freeze-dried is prepared in the form of frozen granules and is processed while being agitated under vacuum.

However, both of the aforesaid methods suffer from certain disadvantages, a primary one being the necessity for a high vacuum system. High vacuum systems inherently require large vacuum pumps, and the drying chamber itself must be exceedingly heavy and of great structural strength in order to Withstand the external pressure of fifteen pounds per square inch. Furthermore, the system must be maintained vacuum-tight. In addition, the effectiveness of the vacuum system may be drastically diminished in situations where the straight line passage of water vapor to the trap in the vacuum system is prevented. 7

It has been shown that the process of freeze-drying, or the removal of water vapor from a frozen specimen by sublimation, can be divided into three steps. The first of these is the transfer of water from the ice crystal to the vapor phase. This is an endothermic process requiring the input of energy in the form of heat. The first requirement for the eflicient carrying out of freeze-drying is that heat must be introduced to the drying boundary to support the sublimation of water vapor. The second step is the transfer of Water vapor from the vicinity of the ice crystal at the drying boundary through the shell of already dried material to the surface of the specimen. This net transfer of water vapor will take place only if the water vapor pressure at the surface of the specimen is lower than that at the drying boundary. In other words, the motion of water vapor will take place only along a water vapor pressure gradient. Since the resistance to diffusion of the dried shell is fixed by other considerations, to obtain efficiency of freeze-drying it is necessary to reduce the partial pressure of water vapor at the specimen surface to the minimum possible level. This is accomplished by the third step in drying which is the removal of water vapor from the specimen surface to maintain the low vapor pressure. This is conventionally done by means of a high vacuum system. The purpose of the high vacuum is to reduce the resistance to vapor flow from the specimen surface to the means of removal of water vapor from the system. This is most generally a low temperature surface which condenses water vapor from the atmosphere. The reduction of absolute pressure within the chamber increases the mean free path for water vapor so that Water molecules traveling from the specimen surface will suffer fewer collisions with other molecules during their travel from the specimen surface to the condensing surface. I have determined that even though a perfect vacuum were achieved in the drying chamber, when the sublimation of ice is initiated the water vapor which emanates from the specimen will create a significant concentration of molecules in the space between specimen and condenser so that they will, in effect, become obstacles to their own net transfer.

I have further determined that the primary usefulness of the high vacuum system is to merely assist in the transfer of water vapor from the specimen surface to the condenser (step three). The transfer of water vapor from the drying boundary to the surface of the specimen (step two) is primarily effected by the water vapor pressure gradient across the dried shell. I have further determined that the dried shell constitutes the principal obstacle to vapor transfer. Accordingly, I have determined that the presence or absence of a vacuum in the specimen chamber is of relatively minor importance in the efliecient transfer of vapor from drying boundary to specimen surface.

This invention has as an object the provision of a process for freeze-drying at atmospheric pressure.

This invention has as another object the provision of a freeze-drying process in which the retention of a relatively high percentage of volatiles in the dried material is possible.

This invention has as still another object the provision of a freeze-drying process which is capable of drying a wide variety of materials including labile materials such as blood plasma or its components or pharmaceuticals, without the loss of chemical integrity.

This invention has as a still further object the provision of a process for freeze-drying materials on a large-scale production at relatively low cost, such as the freeze-drying of a wide variety of foodstuffs, such as milk, juices, soups, coffee extract, and solids such as meats or vegetables.

Other objects will appear hereinafter.

In the process of the present invention a stream of dry air or dry inert gas is flowed past the specimen or material being freeze-dried so as to in effect sweep away Water molecules which reach the surface of the specimen from its interior. In the process of my invention the transfer of water vapor from the vicinity of the ice crystal at the drying boundary through the shell of the already dried material to the surface of the specimen is achieved by a very thorough drying of the air which flows across the specimen. In this manner, -I have determined that it is possible at atmospheric pressure to create a partial pressure of water vapor at the specimen surface which approaches zero and simultaneously to remove effectively water molecules as they reach the specimen surface.

The process of my invention secures other advantages over and beyond conventional vacuum freeze-drying tech 'niques besides the elimination of the need for the cumbersome, massive, and expensive high vacuum system. Thus, in the process of my invention the heat transfer may be introduced by conduction from the flowing drying gas. The drying gas can be flowed over all of the surfaces of the drying specimen 'so that the specimen is never shielded from the source of heat. This is in marked contrast to vacuum systems in which the heat which must support sublimation must be supplied either by conduction through the frozen portion of material dried in bulk, or must be introduced by radiation through the dried shell of the material. It is evident that such systems suffer from the defects in heat transfer of the specimen being shielded from the source of heat in the case of radiation drying or the necessity for drying the specimen from only one side in order to introduce heat by conduction through the frozen bottom.

In the process of my invention, temperature control of the air which flows through the drying chamber is easily achieved, and it is possible to therefore have absolute knowledge of the temperature of the specimen surface, which is not possible in a radiation system.

In the case of materials which have a dry spongy st-ruc ture with poor thermal conductivity, the use of high vacuum, with the resultant high vacuum in the interstices of such material, will result in a thermal insulator. With such materials, the insulation to heat transfer afforded by the dried shell is substantially reduced by the absence of the vacuum.

' The material to be freeze-dried in accordance with the process of my invention should be granulated, and preferably should be relatively finely granulated. The

size of the granules is a prime factor in determining the rate of freeze-drying. The top limit for the size of the granules will vary depending on the nature of the material being dried, but generally the granules should be no larger than half-inch cubes, and preferably appreciably smaller than this. Thus, I have found that with relatively large size granules, it, is diflicult to :get the drying gas around the granules in order to effect drying and moreover the time requirements needed to eflfect penetration are greatly increased.

'The drying gas should, of course, be non-reactive with the material being dried. Where practical, air is the preferred drying gas. However, in situations where oxidation is a problem, an inert gas maybe used as the drying gas.

Q The drying [gas may be dried by a variety of techniques, and then recirculated. Two suitable techniques for drying the drying gas are the use of a desiccant, and the use of a refrigerated condenser, although if desired, both the use of 1a desiccant and refrigerated condenser a single system may be efiected. If a desiccant is utilized, it should have a very low vapor pressure and high water capacity, and be non-reactive with the drying gas. If a refrigerated condenser system is used to remove moisture from the drying gas, it should be associated with a subsequent heat-exchanger for restoring the drying gas to the operating temperature.

For the purpose of illustrating the invention there is shown in the drawings a form which is presently preferred; it beingunderstood, however, that this invention is 'not limited to the precise arrangements and instru- 7 mentalities shown.

The accompanying drawing is a schematic diagram of one form of the embodiment which may be utilized in connection with the process of the present invention.

In the illustrated embodiment, the freeze-drying apweight low-strength material, because in contradistinction to apparatus used in conjunction with high vacuum, no

appreciable degree of strength is required.

The inlet port 14 is in communication with a duct 16, which'extends into the tubular drying chamber 18, which is perpendicularly disposed in respect to the duct 16.

The closure member serves the dual function of sealing off the duct 16 and supporting the material holder 22, which may be in the shape of an open mesh basket or the like. a

The drying chamber 18 flares outwardly into the blower or prime mover 24, which may be a conventional squirrel cage blower driven by the motor 26 which is coupled to the blades of the .blower 24 through the sealed bearing 28.

The flow of drying gas through the freeze-drying apparatus is in the direction shown by the arrows.

The desiccant inventory 30 is designated by the cross hatch lines, with the flow of gas through the desiccant being from the blower 24 through the opening 32, and thence through the desiccant 30, and then through the opening 34 into the drying chamber 18.

A wide variety of materials may be used as desiccants, suitable examples being the zeolites designated as Molecular Sieve, calcium chloride, etc.

A thermocouple 36 may be positioned within the drying chamber 18 to permit accurate control of the air temperature.

Cooling of the air in the freeze-drying apparatus 10 is accomplished by enclosure of said apparatus within a cold chamber 38 which is provided with cooling coils 40 connected to a refrigerating unit 42. The refrigerating unit 42 is in turn controlled by the thermocouple which is connected to the refrigerating unit by suitable electrical leads 44. r

In place of the desiccant 30, a refrigerated condenser plate, such as' one operating at minus 60 C., may be utilized to remove the moisture from the drying gas.

The use of atmospheric gas for drying avoids the removal of gaseous or volatile components other than those which the user intends to specifically remove. Thus, in conventional freeze-drying there is no control over the removal of the volatile components, and generally all of' substantially all of the volatile components are removed. However, in the subject process, the :gas to be used for drying can be adjusted in its composition to have a reduced vapor pressure only for those components which are to be intentionally removed.

In order to illustrate the process of the present invention, there is set forth the following examples, which "serve the purpose of illustration and not for limitation. Thus, it is to be understood that the parameters utilized in the following examples are solely those which were employed in the specific examples there-involved, and that such parameters may be varied to meet specific circumstances.

Example I It was desired to study the histological integrity of dried mouse kidney. To this end, a cube of mouse kidney measuring two millimeters on a side was freshfrozen by immersion in liquid propane at minus-195 C. and dried at minus 30 C. It was found that drying at a higher temperature permitted excessive ice crystal growth, which impaired the histological integrity of the specimen. It was found that desiccation of the specimen ,could be achieved using air in the apparatus shown in the accompanying drawing in eight hours. This is justsome- ;What -slower than the minimum of six hours of drying time required to effect desiccation of the same specimen m an efliciently designed vacuum freeze-drying system.

In order to test for histological integrity, the specimen, ,was removed'after drying in accordance with the process of the present invention to a vacuum chamber for imbedding paraflin. The quality of the results, in terms of histological detail, appears equivalent to that of results obtained by the conventional vacuum freeze-drying approach. In fact, comparative testing revealed that the efficiency of the method of the present invention compared favorablywith the best vacuum freeze-drying, and

was substantially superior to vacuum freeze-drying effected in systems which do not have a cold trap in the line of sight from the specimen.

Example II 57 grams of prefrozen granular beefsteak meat ground to hamburger proportions and disposed in a disk having a thickness of one and one-eighth inches was freeze-dried in accordance with the process of the present invention from a water content of 68.9 weight percent to a Water content of 4.79 weight percent in ten hours. The air temperature used to effect the drying was maintained between 2 C. and 4 C., while the ground beefste-ak was maintained during drying at a temperature of minus 5 C. The air was desiccated by contact with a refrigerated condenser plate which lowered its temperature to approximately minus 60 C. From the desiccation stage, the drying air was warmed to the temperature of 2 C. to 4 C. by heat-exchange, and then contacted with the meat, after which the air was passed to the refrigerated condenser.

The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof and, accordingly, reference should be made to the appended claims, rather than to the foregoing specification as indicating the scope of the invention.

I claim:

1. Apparatus for freeze-drying a water-containing material at atmospheric pressure comprising, an elongated container, which is closed at both ends, an elongated tubular member fixedly mounted within said container and spaced therefrom, said tubular member being shorter than said elongaed member and having its opposite ends spaced from the sides and closed ends of said elongated member, a quantity of desiccant between the outside of said tubular member and the inside of said elongated container, blower means within said elongated container constructed and arranged to circulate air through said tubular member and the desiccant, whereby the air is kept moving and dry, a perforate container within said tubular member constructed to hold a quantity of frozen material which is to be dehydrated, and means constructed to maintain the temperature of the circulating air Within the elongated tubular member below freezing.

2. Apparatus for freeze-drying a water-containing material at atmospheric pressure as set forth in claim 1, wherein the air temperature controlling means comprises, a chamber that encloses said elongated member, cooling coils within said chamber, said coils being operatively associated with a refrigerating unit, and a thermocouple within said elongated tubular member for sensing air temperature within the tubular member, said thermocouple being operatively connected with said refrigerating unit to control operation thereof and therefore the temperature of the air within the freeze-drying apparatus.

References Cited in the file of this patent UNITED STATES PATENTS 2,422,536 Finnegan June 17, 1947 2,435,503 Levinson Feb. 3, 1948 2,435,854 Taylor Feb. 10, 1948 2,441,571 Heineman May 18, 1948 2,480,146 Lee Aug. 30, 1949 2,480,954 Palmer Sept. 6, 1949 2,527,542 Gilson Oct. 3 1, 1950 2,564,475 Fischer Aug. '14, 1951 2,705,678 Morrison Apr. 5, 1955 3,031,381 Langerhans Apr. 24, 1962 

1. APPARATUS FOR FREEZE-DRYING A WATER-CONTAININGG MATERIAL AT ATMOSPHERIC PRESSURE COMPRISING, AN ELONGATED CONTAINER, WHICH IS CLOSED AT BOTH ENDS, AN ELONGATED TUBULAR MEMBER FIXEDLY MOUNTED WITHIN SAID CONTAINER AND SPACED THEREFROM, SAID TUBULAR MEMBER BEING SHORTER THAN SAID ELONGATED MEMBER AND HAVING ITS OPPOSITE ENDS SPACED FROM THE SIDES AND CLOSED ENDS OF SAID ELONGATED MEMBER, A QUANTITY OF DESICCANT BETWEEN THE OUTSIDE OF SAID TUBULAR MEMBEER AND THE INSIDE OF SAID ELONGATED CONTAINER, BLOWER MEANS WITHIN SAID ELONGATED CONTAINER CONSTRUCTED AND ARRANGED TO CIRCULAR AIR THROUGH SAID TUBULAR MEMBER AND THE DESICCANT, WHEREBY THE AIR IS KEPT MOVING AND DRY, A PERFORATE CONTAINER WITHIN SAID TUBULAR MEMBER CONSTRUCTED TO HOLD A QUANTITY OF FROZEN MATERIAL WHICH IS TO BE DEHYDRATED, AND MEANS CONSTRUCTED TO MAINTAIN THE TEMPERATURE OF THE CIRCULATING AIR WITHIN THE ELONGATED TUBULAR MEMBER BELOW FREEZING. 